Gut bacteria affect brain health

Gut bacteria affect brain health

Gut bacteria affect brain health

Abstract: Gut bacteria influence the behavior of immune cells throughout the body and in the brain, including those implicated in neurodegenerative disorders such as Alzheimer’s disease. The findings open up the possibility of altering the microbiome to prevent or treat neurodegeneration.

Source: WUSTL

A growing body of evidence shows that the tens of trillions of microbes that normally live in our intestines – the so-called gut microbiome – have far-reaching effects on how our bodies function. Members of this microbial community produce vitamins, help us digest food, prevent the overgrowth of harmful bacteria, and regulate the immune system, among other benefits.

Now, a new study suggests that the gut microbiome also plays a key role in our brain health, according to researchers at Washington University School of Medicine in St. Louis. Louis.

The study, conducted in mice, found that gut bacteria — in part by producing compounds like short-chain fatty acids — influence the behavior of immune cells throughout the body, including those in the brain that can damage brain tissue and worsen neurodegeneration in conditions such as Alzheimer’s disease.

The findings, published Jan. 13 in the journal Scienceopen the possibility of reshaping the intestinal microbiome as a way of preventing or treating neurodegeneration.

“We gave young mice antibiotics for just a week, and we saw a lasting change in their gut microbiomes, their immune responses, and how much neurodegeneration associated with a protein called tau they experienced with age,” said senior author David M. Holtzman, MD, Barbara Burton and Reuben M. Morriss III, Distinguished Professor of Neurology.

“What’s exciting is that manipulating the gut microbiome could be a way to have an effect on the brain without putting anything directly into the brain.”

There is increasing evidence that the gut microbiomes of people with Alzheimer’s disease may differ from those of healthy people. But it’s not clear whether these differences are a cause or effect of the disease—or both—and what effect microbiome changes might have on the course of the disease.

To determine whether the gut microbiome plays a causative role, the researchers altered the gut microbiomes of mice predisposed to develop brain damage and Alzheimer’s-like cognitive impairment.

The mice were genetically engineered to express a mutated form of the human brain protein tau, which accumulates and causes neuronal damage and atrophy in their brains by 9 months of age.

They also carried a human variant APOE gene, the main genetic risk factor for Alzheimer’s disease. People with one copy APOE4 variants are three to four times more likely to develop the disease than people with the more common one APOE3variant.

In addition to Holtzman, the research team included gut microbiome expert and co-author Jeffrey I. Gordon, MD, Robert J. Glaser, PhD, University Distinguished Professor and director of the Edison Family Center for Genome Sciences & Systems Biology; first author Dong-Oh Seo, PhD, instructor of neurology; and co-author Dr. Sangram S. Sisodia, professor of neurobiology at the University of Chicago.

When such genetically modified mice were raised under sterile conditions from birth, they did not acquire gut microbiomes, and their brains showed much less damage at 40 weeks of age than the brains of mice with normal mouse microbiomes.

When such mice were raised under normal, non-sterile conditions, they developed normal microbiomes. However, a course of antibiotics at the age of 2 weeks permanently changed the composition of bacteria in their microbiomes. For male mice, it also reduced the amount of brain damage seen at 40 weeks of age.

The protective effects of the microbiome changes were more pronounced in the male mice that carried them APOE3 but in those with high risk APOE4variant, probably due to adverse effects APOE4negated some of the protection, the researchers said. Antibiotic treatment had no significant effect on neurodegeneration in female mice.

“We already know, from studies of brain tumors, normal brain development, and related topics, that immune cells in male and female brains respond very differently to stimuli,” Holtzman said.

“So it’s not very surprising that when we manipulated the microbiome, we saw a gender difference in response, although it’s hard to say exactly what that means for men and women living with Alzheimer’s disease and related disorders.”

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Gut bacteria affect brain health

Further experiments linked three specific short-chain fatty acids—compounds produced by certain types of gut bacteria as products of their metabolism—to neurodegeneration. All three of these fatty acids were scarce in mice with gut microbiomes altered by antibiotic treatment and were not measurable in mice without gut microbiomes.

These short-chain fatty acids appear to trigger neurodegeneration by activating immune cells in the bloodstream, which in turn somehow activated immune cells in the brain to damage brain tissue. When middle-aged mice with no microbiome were fed the three short-chain fatty acids, their brain immune cells became more reactive, and their brains showed more signs of tau-related damage.

This shows the outline of the head
There is increasing evidence that the gut microbiomes of people with Alzheimer’s disease may differ from those of healthy people. The image is in the public domain

“This study may offer important insights into how the microbiome affects tau-mediated neurodegeneration and suggest therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders,” said Dr. Linda McGavern, program director at the National Institute of Neurological Disorders . and Stroke (NINDS), which provided part of the funding for the study.

The findings point to a new approach to the prevention and treatment of neurodegenerative diseases by modifying the gut microbiome with antibiotics, probiotics, specialized diets or other means.

“What I want to know is, if you took mice genetically predisposed to develop a neurodegenerative disease, and you manipulated the microbiome just before the animals started showing signs of damage, could you slow down or prevent neurodegeneration?” Holtzman asked.

“This would be equivalent to starting treatment on a person in late middle age who is still cognitively normal but on the verge of developing impairment. If we could start treatment in these types of genetically sensitized adult animal models before the neurodegeneration first becomes apparent, and show that it works, that might be the kind of thing we could test in humans.

About this microbiome and neuroscience research news

Author: Judy Martin Finch
Source: WUSTL
Contact: Judy Martin Finch – WUSTL
Picture: The image is in the public domain

Original research: Findings will appear in Science


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